The World Health Organization is now advising health care professionals to start patients with HIV on antiretroviral drugs earlier in the course of their infection, as part of new agency guidelines announced Monday.

The new recommendations will likely result in more patients worldwide obtaining treatment, based on their CD4 immune cells counts. Instead of a CD4 cell count of 200, the threshold which the WHO recommended in its 2006 guidelines for HIV treatment, a CD4 cell count at or below 350 should be the cutoff, the agency now advises. In practice, this shift would mean treating HIV-infected patients one or two years earlier. For patients with symptoms of HIV infection, such as weight loss, fever and frequent opportunistic infections, the WHO advises that treatment start immediately, regardless of CD4 count.

Although earlier treatment increases the likelihood of drug side effects and the emergence of drug-resistant viruses, doctors and scientists on the WHO panel for the new guidelines think these risks are outweighed by benefits, namely reducing AIDS-related illnesses and the transmission of HIV. By reducing viral loads in patients, antiretroviral drugs make transmission less likely.

The WHO's guidelines put the worldwide standard for HIV therapy, and in particular in Africa, in step with that of the United States and Europe, where HIV-positive patients with CD4 cell counts of 350 typically are started on therapy.

In creating the new guidelines, which the organization revisits every couple of years, the WHO panel considered national guidelines and international guidelines, as well as relevant clinical studies, says Dr. Siobhan Crowley, who led the WHO's guideline revision process this year. One of the studies, published in 2008, suggested that patients whose antiretroviral treatment was deferred until their CD4 cell counts were below 250 were at greater risk of opportunistic infection than those that received antiretroviral treatment when CD4 cell counts were higher than 350.

Currently, about four million people worldwide are on antiretroviral drugs with another 5.5 million HIV-positive people awaiting treatment. If countries adopt these guidelines, an additional three to five million people would become eligible to take these drugs, according to the WHO's estimate. Partly because patients do not start to feel sick until their CD4 counts drop to around 200, "over half of those [three to five million] still don't know they have HIV," Crowley says

To raise health awareness, the WHO has been recommending increased HIV testing and monitoring of CD4 levels. Under the new guidelines, HIV-positive patients should have their CD4 levels checked every three to six months, as is the policy in the United States and Europe.

But regular CD4 count monitoring is no trivial matter in many areas of Africa where clinics and trained staff are in low supply and transportation is difficult, says David Ross, a clinical epidemiologist at the London School of Hygiene and Tropical Medicine. "For the guidelines to really be implemented, one's going to have to put in place systems to help people come [to the clinic] to have CD4 count tests," he says.

In spite of the work ahead, Ross agrees with the guidelines. "I think it's the right advice. The big question is, 'Will the money come in?'"

Dr. Crowley says that the WHO will not yet give estimates for the price tag of implementing the new guidelines. The organization asks that each country consider what it can afford and what capacity of treatment it can handle. "Many countries have gone to a sort of middle ground. They've gone to 250 [as the CD4 count cutoff]," she says.

Aid organizations such as the U.S. President's Emergency Plan for AIDS Relief, or PEPFAR, have not committed to increasing their financial support. But, Crowley says, PEPFAR workers did offer advice as the panel developed the guidelines. PEPFAR and the United Nations Joint Programme on HIV/AIDS Unied Budget and Workplan (UNAIDS UBW) funded the panel's work.

Along with raising the bar for treatment overall, the new WHO guidelines shift the advice for treating pregnant women and infants. As with the general population, the organization recommends that all HIV-positive pregnant women begin antiretroviral therapy in their first trimester if their CD4 counts drop to 350 (instead of the previous threshold of 200), and by the second trimester regardless of CD4 count. The current practice in countries in Africa and Asia is to administer HIV treatment in pregnant women several weeks before their delivery date.

"The policies in Africa right now were designed for one purpose and one purpose only—to prevent transmission, but the mother was not part of the equation," says Dr. Aditya Kaul, who is a professor in the Department of Pediatric Infectious Disease at the New York University Langone Medical Center.

The new guidelines also recommend that HIV-positive mothers breastfeed their newborn babies but that the mother or infant be on antiretroviral therapies to prevent the transmission of virus in the milk. As Kaul points out, doctors realized that infants in Africa are healthier on their mother's breast milk even if their mothers are HIV-positive because the milk helps protect babies from other infections. In contrast, the U.S. guidelines, issued by the National Institutes of Health, recommend against HIV-positive women breastfeeding.

When it comes to which antiretroviral drugs it recommends, the WHO guidelines are consistent from 2006 to 2009. The panel continues to recommend a three-part therapy that contains AZT, or the HIV inhibitor called TDF, in the place of stavudine, which can alter fat metabolism and cause nerve damage. Crowley says that the therapy offered will be a country-based decision, taking availability and affordability into account. AZT and TDF are more expensive than stavudine.

In the scheme of what can be a multi-decade treatment regime, Ross (of the London School of Hygiene and Tropical Medicine) says that treating one or two years earlier should not make a big difference in terms of side effects or drug resistant viruses risks. The long-term side effects of HIV drug treatment, such as increased cholesterol and heart disease, that crop up after 10 or 15 years will still occur. But, Kaul points out, these side effects can often be countered by treatment with other medicines, such as statins, or by making lifestyle changes.

Kaul, like Ross, thinks that the change in guidelines is a step in the right direction, and it sends the right message about HIV treatment for people in Africa and Asia. "Unless we put these [new guidelines] in place we will not get to the point that we expect the same care for them as [for people] in the U.S.," Kaul says.

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